Enantioselective hydroformylation

ABSTRACT

Enantioselective hydroformylation of vinyl compounds using a catalyst composition of a chiral carbohydrate phosphorous ligand with a Rh, Pt, Co or Ir metal, to produce chiral 2-substituted propanals, wherein the phosphorous of the ligand is substituted with electron withdrawing groups.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a division of U.S. application Ser. No. 08/116,235filed Sep. 2, 1993, now U.S. Pat. No. 5,475,146.

FIELD OF THE INVENTION

The present invention relates to enantioselective hydroformylation ofvinyl compounds R--CH═CH₂ to produce chiral nonracemic 2-substituted1-propanals of the formula R--CH(CHO)CH₃ ; wherein a catalystcomposition of the reaction comprises Rh, Pt, Co or Ir, and a chiral,nonracemic carbohydrate phosphorous ligand wherein the phosphorus issubstituted with electron withdrawing groups.

BACKGROUND OF THE INVENTION

It is known in the art that optically active diphosphinites derived fromcarbohydrates can be used as ligands for the metals Rh and Pt in theasymmetric hydroformylation of vinyl arenes. The major problem that hasplagued the well-known Pt-catalyzed hydroformylations, however, is theunfavorable branched to linear ratios which reduce overall selectivity.The Rh-catalyzed reactions generally give good branched to linear ratiosbut enantioselectivity is poor. A series of metal/ligand combinationswhich overcome these limitations is the subject of this application.

Ojima, I. and Hirai, K., "Asymmetric Hydrosilylation andHydrocarbonylation" in Asymmetric Synthesis; Morrison, J. D., Ed.;Academic Press, Orlando, Fla., 1985; pp 103-146 and Jackson, W. R. andLovel, C. G., Aust. J. Chem., 35, 2069-75 (1982) describe low asymmetricinduction in the hydroformylation of vinyl acetate in the presence of aphosphinite derived from tartaric acid.

German patents DD280,473, DD275,623 and DD275,671 and references Selkeet al., J. Mol. Cat., 37, 213-225 (1986) and Selke, J. Organometal.Chem., 370, 249-256 (1989) disclose related rhodium carbohydratecatalysts mainly for enantioselective hydrogenation reactions, but noteaching is provided which demonstrates or enables effectiveenantioselective hydroformylation, and the importance of electroniceffects of these ligands is not suggested.

Ligands similar to those used in the present invention are disclosed inRajanBabu, T. V. and Casalnuovo, A. L., J. Am. Chem. Soc., 114,6265-6266 (1992) and U.S. Pat. No. 5,175,335, for use in other catalystcompositions for asymmetric hydrocyanation.

High enatioselectivities are most often explained on the basis of stericarguments, see for example, Brown, J. M., Chem. Soc. Rev., 25 (1993),and references cited therein. For a recent example of the application ofclassical and widely used steric approach to design of enantioselectivecatalysts see: Trost, B. M. et al. J. Am. Chem. Soc. 114, 9327 (1992)and references cited therein. Recently, electronic effects are describedas being effective in enhancing enantioselectivity inmanganese-catalyzed oxidation, Jacobsen, E. N. et al., J. Am. Chem. Soc.113, 6703, (1991), and in nickel-catalyzed hydrocyanations, RajanBabu,T. V. and Casalnuovo, A. L., J. Am. Chem. Soc., 114, 6265-6266 (1992).No teaching of electronic effects in the enantioselectivehydroformylation reaction have been described.

SUMMARY OF THE INVENTION

The present invention provides a process for enantioselectivehydroformylation comprising: reacting a vinyl compound of formula I

    R--CH═CH.sub.2                                         I

with a source of CO and H₂, in the presence of a catalyst compositioncomprising one or more metals selected from the group consisting of Co,Rh, Ir, and Pt, and a chiral, nonracemic ligand of formula II

    (R.sup.1).sub.2 --P--O--R.sub.2 --O--P--(R.sup.1).sub.2    II

to produce a nonracemic hydroformylated product of formula III ##STR1##wherein: R is a C₁ to C₂₀ carboalkoxy, a C₁ to C₄₀ hydrocarbyl, or a C₁to C₄₀ heterocyclic radical; each optionally substituted with one ormore halo, alkoxy, carboalkoxy, hydroxy, amido or keto groups;

each R¹ is an electron-withdrawing group comprising an aromatichydrocarbyl substituted with one or more halo, halogen-substituted alkylgroups, cyano, alkylsulfonyl, carboalkoxy, quaternary ammonium, nitro,amido or keto groups; or a heteroaromatic optionally substituted withone or more halo, halogen-substituted alkyl groups, cyano, alkylsulfonyl, carboalkoxy, quaternary ammonium, nitro, amido or keto groups;

R² is a C₄ to C₄₀ dideoxy carbohydrate optionally substituted with oneor more hydrocarbyl, halo, alkoxy, carboalkoxy, hydroxy, amido or ketogroups.

The present invention also provides a novel catalyst compositioncomprising one or more metals selected from the group consisting of Co,Rh, Ir and Pt, and one or more chiral nonracemic ligands of formula II

    (R.sup.1).sub.2 --P--O--R.sup.2 --O--P--(R.sup.1).sub.2    II

wherein:

each R¹ is an electron-withdrawing group comprising an aromatichydrocarbyl or heteroaromatic, optionally substituted with one or morehalo, halogen-substituted alkyl groups, cyano, alkyl sulfonyl,carboalkoxy, quaternary ammonium, nitro, amido or keto groups; and

R² is a C₄ to C₄₀ dideoxy carbohydrate; optionally substituted with oneor more hydrocarbyl, halo, alkoxy, carboalkoxy, hydroxy, amido or ketogroups.

DETAILED DESCRIPTION OF THE INVENTION

The process of the instant invention, whereby enantioselectivehydroformylation is accomplished by reacting a vinyl compound of theformula R--CH═CH₂ with hydrogen and carbon monoxide in the presence of achiral, nonracemic, metal (Rh, Pt, Ir or Co) hydroformylation catalyst,is useful, for example, to produce 2-substituted-1-propanals. Forexample, vinyl arenes are precursors to nonsteroidal, anti-inflammatorydrugs such as ibuprofen and naproxen. The novel catalyst compositions ofthe instant invention, comprising a metal and chiral, nonracemicdiphosphinite ligand derived from a carbohydrate diol, are useful foraccomplishing the above-described enantioselective hydroformylationreactions.

The enantioselective hydroformylation reaction of the invention isperformed by reacting a vinyl compound of the formula R--CH═CH₂ withhydrogen and carbon monoxide at pressures of about 100-2400 psi (1psi=6.9 kPa) in the presence of a chiral, nonracemic, metal (Rh, Pt, Iror Co) hydroformylation catalyst. These reactions produce chiral,nonracemic, 2-substituted-1-propanals of the formula R--CH(CHO)CH₃,herein called branched aldehydes. Undesired products,3-substituted-1-propanals are also generated, herein called linearaldehydes. The selectivity of this reaction will be reported herein bythe ratio of branched aldehyde (b) to the linear aldehyde (1). ##STR2##

By the term "carbohydrate", Applicants mean the class of organiccompounds comprising the general formula (CH₂ O)_(n), wherein n is equalto or greater than four. The carbohydrate-derived ligands of theinvention are derived from C₄ to C₄₀ carbohydrates includingmonosaccharides, disaccharides and oligosaccharides.

By the term "heterocycle", Applicants mean a cyclic carbon compoundcontaining at least one oxygen, nitrogen or sulfur atom in the ring.

By the term "hydrocarbyl", Applicants include all alkyl, aryl, aralkylor alkylaryl carbon substituents, either straight-chained, cyclic, orbranched, accordingly substituted with hydrogen. The term "hydrocarbyl"as used herein includes both aromatic and nonaromatic hydrocarbyls.

By the term electron-withdrawing group, Applicants include those groupsthat have σ-values (any, σ-values such as σ_(p), σ_(m), σ_(I), σ_(R),etc.) greater than or equal to 0.1 (as defined by the Hammett equation,see for example March, J. Advanced Organic Chemistry, Reactions,Mechanisms, and Structure, 4th ed.; 1992, Wiley: New York, pp 278-286).

In describing a carbohydrate group of the formula O--R² --O, as itappears within the ligand of the present disclosure, the group R² isnamed by using the prefix "dideoxy" with the name of the parent diol ofthe formula HO--R² --OH. For example, the name 2,3-dideoxyglucose refersto the group: ##STR3## and accordingly, the corresponding carbohydrategroup O--R² --O is: ##STR4##

The suffix -ose- when used in combination with carbohydrate root names,shall include those compounds wherein the OH groups are protected asethers or esters. By this definition, for example, the glucopyranosidestructure shown below is termed "a glucose" ##STR5## wherein Ac is anacetyl.

By the term "chiral", Applicants mean "existing as a pair ofenantiomers". These enantiomers, where the chiral centers are designatedthe R and S isomers, are nonsuperimposable mirror images of one another.A chiral material may either contain an equal amount of the R and Sisomers in which case it is called "racemic" or it may containinequivalent amounts of R and S isomer in which case it is called"optically active", or "nonracemic".

By the term "enantiomeric excess" ("ee"), Applicants mean theabsolute-difference between the percent of R enantiomer and the percentof S enantiomer of an optically active compound. For example, a compoundwhich contains 75% S isomer and 25% R isomer will have an enantiomericexcess of 50%.

By the term "enantioselective" Applicants mean the ability to produce aproduct in an optically active form.

The substrates of the invention are described by the formula R--CH═CH₂,where R may be any C₁ to C₂₀ carboalkoxy, C₁ to C₄₀ hydrocarbyl or C₁ toC₄₀ heterocyclic radical; each of which may be substituted with one ormore halo, alkoxy, carboalkoxy, hydroxy, amido or keto groups. Examplesof R include, but are not limited to, phenyl, substituted phenyl,polyaromatic (e.g., naphthyl, anthryl), substituted polyaromatic,acetoxy, alkyl and substituted alkyl. Representative examples ofsubstrates used in the invention include, but are not limited to,2-vinylnaphthalene, 6-methoxy-2-vinylnaphthalene, vinyl acetate,4-isobutylstyrene, 4-methylstyrene and styrene.

The vinyl substrates of the invention may be made by methods which arewell-known in the art e.g., Organometallics, 10, 1183-1189 (1991), whichis hereby incorporated by reference. Many substrates are also availablecommercially.

The chiral, nonracemic carbohydrate diphosphinite ligands of theinvention are defined as (R¹)₂ --P--O--R² --O--P--(R¹)₂, wherein R¹ maybe an aromatic hydrocarbyl substituted with one or more halo,halogen-substituted alkyl groups, cyano, alkyl sulfonyl, carboalkoxy,quaternary ammonium, nitro, amido or keto groups; or a heteroaromaticoptionally substituted with one or more halo, halogen-substituted alkylgroups, cyano, alkyl sulfonyl, carboalkoxy, quaternary ammonium, nitro,amido or keto groups. These ligands are unique in this art in that theR¹ group of the ligand is an electron-withdrawing group as definedherein. Applicants have discovered that electron-withdrawing groupsgenerally lead to high selectivity in the hydroformylation method ofthis invention.

For all embodiments of the Applicants' invention, the chiral,nonracemic, metal hydroformylation catalyst composition comprises achiral, nonracemic, carbohydrate diphosphinite ligand and a source ofone or more of the metals Rh, Pt, Co and It. Suitable sources of therhodium, platinum, cobalt, and iridium include, but are not limited to,the metal halides, olefin complexes, acetoacetates, and carbonyls. Metalcompounds that contain ligands which can be displaced by the chiralcarbohydrate phosphorus ligand are a preferred source of the metal. Inthe case, for example, of rhodium (I) intermediates, (COD)₂ RhX species(COD is 1,5-cyclooctadiene) are the precursors of choice, with thecounterion X being tetrafluoroborate (BF₄), antimony hexafluoride(SbF₆), or trifluoromethanesulfonate (OTf); although other counterionssuch as tetraphenylborate (BPh₄) and perchlorate (ClO₄) would also besuitable. Chiral iridium compounds can be prepared from [(COD)IrCl]₂.Platinum compounds can be synthesized fromdichloro-bis(benzo-nitrile)platinum (II). Cobalt compounds can beprepared from cobalt carbonyl. Rhodium is the preferred metal.

The catalyst composition also employs a ligand comprising a chiral,nonracemic diphosphinite of the formula (R¹)₂ --P--O--R² --O--P--(R¹)₂,wherein the R² is a C₄ to C₄₀ dideoxycarbohydrate, optionallysubstituted with one or more hydrocarbyl, halo, alkoxy, carboalkoxy,hydroxy, amido or keto groups; and such that the fragment of the liganddefined by the structure PO--R² --OP is chiral. By this definitionApplicants intend that the chirality of the diphosphinite ligand arisesfrom the chirality of the parent carbohydrate diol HO--R² --OH.

Specifically, the process is carried out by employing chiral,nonracemic, O-substituted carbohydrate phosphorus ligands; includingparticularly pyranose, furanose, disaccharide and oligosaccharideorganophosphorus ligands. Examples are represented by the formulas IV,V, VI and VII, ##STR6## wherein: n=0-2;

m=0-3;

R⁴ groups are independently H, hydroxy, C₁ to C₂₀ hydrocarbyl, alkoxy,aryloxy, O-substituted pyranose or O-substituted furanose;

R⁵ groups are independently H, hydroxymethyl (CH₂ OH), alkoxymethyl,aryloxymethyl, or CH₂ OP(X)₂ where X is aryl, alkoxy, or aryloxy;

R⁶ groups are independently H, C₁ to C₂₀ hydrocarbyl, acyl, or P(X)₂where X is aryl, alkoxy, or aryloxy;

R⁷ is H or CH₃ ;

and the sum total of P(X)₂ groups present in the O-substituted pyranose,furanose, dissacharide or oligosaccharide organophosphorus ligand isequal to 2.

Applicants also specifically include within the carbohydrate ligandcompositions of the invention those carbohydrates containing protectivegroups. By the term "protective group", Applicants include groups suchas ethers and esters which function to provide chiral recognition of thesugar molecule, and further are commonly employed to protect the sugarmolecule from nonselective reactions. Applicants further intend toparticularly include disaccharides formed by joining two of thestructures shown in formulas IV-VII through an oxygen atom at theanomeric position of the furanose or pyranose ring. Two examples of suchdissacharides are shown below, wherein Ph is phenyl and Ac is acetyl.##STR7##

Most preferably, the chiral, nonracemic, organophosphorus ligand is achiral, nonracemic, O-substituted glucopyranose organophosphorus ligandof the formula VIII, ##STR8## wherein: R⁸ is H, hydroxy, C₁ to C₂₀hydrocarbyl, alkoxy, or aryloxy;

R⁹ is independently selected from H, C₁ to C₂₀ hydrocarbyl, acyl orP(X)₂, where X is aryl, alkoxy, aryloxy;

and the sum total of P(X)₂ groups present in the O-substitutedglucopyranose organophosphorus ligand is equal to 2.

Chiral, nonracemic O-substituted carbohydrate derived diolphosphorusligands can be prepared according to techniques well-known in the art.[J. Organomet. Chem., 159, C29 (1978); Tetrahedron Lett., 1635 (1978);J. Org. Chem., 45, 62 (1980); Bull. Chem. Soc. Jpn., 59, 175 (1986); J.Mol. Catal., 37, 213 (1986); J. Prakt. Chem., 329 (4), 717 (1987)]. Ingeneral, diol derivatives containing unprotected hydroxyl groups aretreated with a P(R)₂ Cl (wherein R may generally be an alkyl, aryl,alkoxy, or aryloxy) reagent, in the presence of a base, such as pyridineor triethylamine, to produce the desired phosphinite or phosphite. SomeP(R)₂ Cl reagents are commercially available, such as PPh₂ Cl(Ph=phenyl). Other P(R)₂ Cl reagents, where R=aryl or alkyl, can beprepared by two methods. Method A involves the reaction of(amino)dichlorophosphines such as Et₂ NPCl₂ with RMgBr followed byreaction with HCl [J. Am. Chem. Soc. 2148, 82, (1960)]; J. Am. Chem.Soc. 80, 1107 (1958). Alternatively, treatment of readily availabledialkyl phosphites, such as dibutyl phosphite, HP(O)(OBu)₂, with RMgBrfollowed by reaction with PCl₃ provides P(R)₂ Cl derivatives. [J. Am.Chem. Soc. 73, 4101 (1951); J. Am. Chem. Soc., 74, 5418 (1952)]; J. Org.Chem., 31, 1206 (1966). P(R)₂ Cl reagents, where R=alkoxy or aryloxy,can be prepared in two steps by treatment of P(NEt₂)₃ with ROH togenerate P(OR)₂ (NEt₂), followed by treatment with CH₃ COCl to generateP(OR)₂ Cl. Illustrative preparations are provided below.

For all embodiments of the invention the chiral, nonracemic metalhydroformylation catalyst may be prepared by mixing the metal source andthe chiral, nonracemic, organophosphorus ligand, preferably in asuitable organic solvent under an inert atmosphere such as N₂ or Ar in atemperature range from 0° C. to 120° C., preferably in a temperaturerange from 0° C. to 80° C. The metal compound may be used in thissolution or the metal compound can be obtained in the pure form uponremoval of the solvent.

The molar ratio of chiral, nonracemic, organophosphorus ligand to themetal may vary between 1:1 to 10:1, preferably between 1:1 to 1.2:1.

The molar ratio of metal complex to vinyl compound may vary between0.0001:1 to 1:1, preferably between 0.0025:1 to 0.05:1.

The vinyl compound starting material, which is represented by theformula R--CH═CH₂ may be dissolved in any organic solvent compatiblewith the reagents employed, preferably a nonpolar solvent (nonpolarsolvents generally provide higher ee's) such as, but not limited to,benzene, hexane, or triethylsilane. In the case of a liquid substrate,the substrate itself can serve as the solvent.

The H₂ and CO can be provided by contacting the reaction mixture withthe gases and can be provided in mixtures of H₂ to CO ranging from 10:1to 1:10.

A preferred 1:1 mixture of H₂ and CO can be conveniently prepared orpurchased commercially. The pressures of H₂ and CO under which thehydroformylation reactions can be conducted range generally from100-2400 psi (1 psi=6.9 kPa), with 500-1000 psi being the preferredpressure. The pressure employed is not critical; for example, in thecase of the hydroformylation of 2-vinylnapthalene in hexane at roomtemperature using catalyst 1, the following ee's were obtained with thepressure of H₂ and CO (1:1) indicated: 49% (500 psi), 51% (1600 psi),and 31% (2400 psi).

The hydroformylation reaction is preferably carried out over atemperature range from 20° to 80° C., most preferably 25° to 30° C.Applicants note that the observed overall selectivity (ee's and branchedto linear ratios) generally decreases as the temperature is increased.For example, the hydroformylation of 2-vinylnapthalene in benzene at1600 psi provides an ee of 10% when the reaction is performed at roomtemperature and 1% at 70° C. The branched to linear ratio in this casefalls from 21:1 (room temperature) to 12:1 (70° C.). In addition, the eeof the hydroformylation of 2-vinylnapthalene decreases from 12% to 11%when the reaction is conducted in THF at room temperature versus 70° C.The branched to linear ratio also decreases in the latter example from40:1 (room temperature) to 10:1 (70° C.).

The enantioselective hydroformylation reactions are generally completewithin 18-48 hours. In the case of platinum catalysts, the presence of aLewis acid such as tin (II) chloride is typically preferred.

To demonstrate a preferred mode of the invention which produces aparticularly useful product, preparation of optically active(S)-(-)-2-(6-methoxy-2-naphthalene)propanal, can be achieved. Thecatalyst composition comprises a cationic rhodium (I) compound and theligand of formula II wherein each R¹ is the aryl group3,5-bis(trifluoromethyl)phenyl and R² is the O-substitutedβ-D-glucopyranose derivative of the formula IX, the starting vinylcompound is 6-methoxy-2-vinylnaphthalene, and the preferred source ofthe rhodium(I) species is (COD)₂ RhBF₄. ##STR9##

For the preparation of optically active(S)-(-)-2-(6-methoxy-2-naphthalene)propanal, the enantioselectivehydroformylation is preferably carried out at 25° C. under 500 p.s.i.pressure of a 1:1 mixture of H₂ and CO. A mixture of6-methoxy-2-vinylnapthalene and the chiral rhodium complex in anon-polar organic solvent such as benzene, hexane, or triethylsilane isshaken at room temperature for 18 h. In this preferred embodiment amolar ratio between 0.0025:1 to 0.05:1 of rhodium catalyst to vinylcompound is preferred. A molar ratio between 1:1 to 1:1.2 of metal toorganophosphorus ligand is preferred.

Using these preferred conditions an ee between 35-72% of the Senantiomer of 2-(2-naphthyl)propanal and a yield between 75-95% willgenerally be obtained. Isolation of the product aldehyde can be achievedby flash column chromatography of the reaction mixture on silica gelusing 10% diethyl ether/hexane as eluent.

General Procedures for the Preparation of Chiral, O-SubstitutedCarbohydrate Phosphinite and Phosphite Ligands ##STR10## Ligand 1; R¹=3,5-(CF₃)₂ C₆ H₃ Ligand 2; R¹ =Ph (phenyl)

Ligand 3; R¹ =4-FC₆ H₄

Ligand 4; R¹ =(4-CF₃)C₆ H₄

The ligands 1 through 4 above were prepared according to the methodpreviously reported in U.S. Pat. No. 5,175,335, which is herebygenerally incorporated by reference. However, a modified procedure forthe synthesis of Ar₂ PCl (ligand 5) was developed (see below). Allreactions were carried out under a N₂ atmosphere using standard Schlenktechniques or a Vacuum Atmospheres Co. Drybox. Solvents were distilledand degassed prior to use.

Example of Modified Procedure for Synthesis of Ligand 5, Ar₂ PClSpecies; Di-[(3,5-bis-trifluoro-) methyl)phenyl]chlorophosphine

A 1.0M solution of (3,5-bis-trifluoromethyl)phenylmagnesium bromide wasprepared in the dry box by slow addition of 18.5 g (60 mmol) of(3,5-bis-trifluoromethyl)bromobenzene in 40 mL of THF to a slurry of Mgturnings in 20 mL of THF. After 1 h, this solution was added slowly to asolution of 5.0 g (29 mmol) of Et₂ NPCl₂ in 30 mL of THF at 0° C. After2 h, the mixture was concentrated in vacuo. Cyclohexane (100 mL) wasadded and the mixture was filtered to provide a solution of [di-3,5-bis(trifluoromethyl)-phenyl](diethylamino)phosphine. Dry HCl waspassed through this solution for 1 h. After filtration andconcentration, 12.4 g (88%) ofdi-[(3,5-bis-trifluoromethyl)-phenyl]chlorophosphine was collected as awhite solid. ³¹ P (C₆ D₆) δ70.4, s. ¹ H (C₆ D₆) δ7.54 (s, 1) 7.66 (d, 1,J=7 Hz).

SYNTHESIS OF CATALYSTS ##STR11## Catalyst 1: Ar=3,5-(CF₃)₂ C₆ H₃ ; A=BF₄(Phenyl2,3-bis-O-{[di-(3,5-bis-trifluoro-methyl)phenyl]phosphino}-4,6-benzylidene-β-D-glucopyranoside)-(1,5-cyclooctadienyl)Rhodium(I) Tetrafluoroborate

To a solution of 89 mg (0.22 mmol) of (COD)₂ RhBF₄ in 2 mL of CH₂ Cl₂was added a solution of 300 mg (0.24 mmol) of ligand 1 in 2 mL of CH₂Cl₂. After 30 min, the mixture was concentrated to give a 2:1 mixture ofcomplexes of catalyst 1. Major complex showed: ³¹ P NMR δ126.7 (dd, 1,J=40, 184 Hz), 123.0 (dd, 1, J=40, 179 Hz); Minor complex showed: ³¹ PNMR δ139.7 (dd, 1, J=48, 234 Hz), 124.1 (dd, 1, J=48, 240 Hz).

Catalyst 2: Ar=Ph; A=BF₄ (Phenyl2,3-bis-O-diphenylphosphino)-4,6-benzylidene-β-D-glucopyranoside)-(1,5-cyclooctadienyl)Rhodium(I) Tetrafluoroborate

In a similar fashion, catalyst 2 was prepared from 31 mg of (COD)₂ RhBF₄and 57 mg of ligand 1. Catalyst 2 showed: ³¹ P NMR δ134.5 (dd, 1, J=28,179 Hz), 137.5 (dd, 1, J=28, 178 Hz).

Catalyst 3: Ar=3,5-(CF₃)₂ C₆ H₃ ; A=OSO₂ CF₃ (Phenyl2,3-bis-O-{[di-(3,5-bis-trifluoro-methyl)phenyl]phosphino}-4,6-benzylidene-β-D-glucopyranoside)-1,5-cyclooctadienyl)rhodium(I) Trifluoromethanesulfonate

In a similar fashion, catalyst 3 was prepared from 40 mg of (COD)₂Rh(OSO₂ CF₃) and 100 mg of ligand 1. Catalyst 3 showed: ³¹ P NMR δ122.6(dd, 1, J=44, 176 Hz), 126.0 (dd, 1, J=44, 166 Hz).

Catalyst 4: Ar=4-FC₆ H₄ ; A=BF₄ (Phenyl{2,3-bis-O-[di-(4-fluorphenyl)-phosphino]}-4,6-benzylidene-β-D-glucopyranoside)(1,5-Cyclooctadienyl)rhodium (I) Tetrafluoroborate

In a similar fashion, catalyst 4 was prepared from 49 mg (0.121 mmol) of(COD)₂ RhBF₄ and 100 mg (0.128 mmol) of 3. Catalyst 4 showed: ³¹ P(CDCl₃) δ131.3 (dd, 1, J=30, 181), 136.0 (dd, 1, J=32, 179 Hz).

Catalyst 5: Ar=3,5-(CF₃)₂ C₆ H₃ ; A=SbF₆ (Phenyl(2,3-bis-O-{[di-(3,5-bis-trifluoro-methyl)phenyl]phosphino}-4,6-benzylidene-β-D-glucopyranoside)-(1,5-cyclooctadienyl)Rhodium (I) Hexafluoroantiomanate

In a similar fashion, catalyst 5 was prepared from 42 mg (0.076 mmol) of(COD)₂ RhSbF₆ and 100 mg (0.080 mmol) of ligand 1. A ca. 4:1 mixture ofcomplexes of catalyst 5 was obtained. Major complex showed: ³¹ P NMRδ0.126.6 (dd, 1 J=34, 182 Hz), 130.7 (dd, 1, J=34, 186 Hz); Minorcomplex showed: ³¹ P NMR δ125.6 (dd, 1, J=44, 239 Hz), 139.8 (dd, 1,J=44, 236 Hz).

Catalyst 6: Ar=(4-CF₃)C₆ H₄ ; A=BF₄ (Phenyl(2,3-bis-O-{[di-(4-trifluoromethyl)-phenyl]phosphino}-4,6-benzylidene-.beta.-D-glucopyranoside)-(1,5-cyclooctadienyl)Rhodium (I) Tetrafluoroborate

A solution of catalyst 6 was prepared in situ from ligand 4 and (COD)₂RhBF₄. ##STR12##

Catalyst 7: Ar=Ph {(Phenyl[2,3-bis-O-(diphenylphosphino)]-4,6-benzylidene-β-D-glucopyranoside}platinum(II) Dichloride

To a solution of 50 mg (0.11 mmol) of (PhCN)₂ PtCl₂ in 3 mL of benzenewas added a solution of 90 mg (0.13 mmol) of ligand 2 in 2 mL ofbenzene. After 1 h, the mixture was filtered through a glass wool plugand concentrated to give catalyst 7: ³¹ P NMR δ95.1 (d, 1, J=11 Hz),94.4 (d, 1, J=11 Hz).

Catalyst 8: Ar=3,5-(CF₃)₂ C₆ H₃ {(Phenyl{[di-(3,5-bis-trifluoromethyl)-phenyl]phosphino}-4,6-benzylidene-β-D-glucopyranoside}platinum(II) Dichloride

A solution of catalyst 8 was prepared in situ from ligand 1 and (PhCN)₂PtCl₂.

Catalyst 9: Chiral Iridium Catalyst Preparation of Chiral IridiumCatalyst

To a solution of 50 mg (0.074 mmol) of [Ir(COD)Cl]₂ in 5 mL of CH₃ CNwas a added a solution of 198 mg (0.158 mmol) of ligand 1 in 5 mL of CH₃CN. After 1 h, the solution was concentrated to give catalyst 9 as ayellow-orange powder.

Catalyst 10: Chiral Cobalt Catalyst

Chiral cobalt catalyst 10 was generated in situ from 4 mg of Co₂ (CO)₈and 22 mg of ligand 1 in 2 mL of THF.

EXAMPLES 1-36 General Methods for Enantioselective Hydroformylation ofVinyl Compounds, for Examples 1-36

Results and reaction conditions for the enantioselectivehydroformylation of vinyl compounds are shown in Tables I-IV. With a fewexceptions which are noted, the hydroformylations were conducted byshaking a solution of the vinyl compound under a pressure of H₂ and COat the noted temperature. Conversions were determined by integration ofthe formyl protons of the product aldehydes and the vinyl protons of thevinyl compounds in the ¹ H NMR spectrum of the crude product mixture.EE's were determined after reduction of the crude mixture with lithiumaluminum hydride to generate the corresponding primary alcohols by HPLCusing a Bakerbond Chiral DNBPG Chiralcel OJ or OB column (J. T. Baker,Phillipsburg, N.J.): 2-5% i-PrOH/Hexane, 1 mL/min., 40° C. HPLC sampleswere passed through a short pad of silica gel and eluted with ahexane/Et₂ O gradient prior to analysis. In some instances ee's weredetermined by ¹ H NMR using chiral shift reagent Eu(hfc)₃ or by gaschromatographic separation using a Chiraldex G-TA capillary column(Aztec, Whippany, N.J.). EE values refer to an excess of theS-enantiomer. Enriched samples of the S-alcohols from thehydroformylation of 2-vinylnapthalene and 6-methoxy-2-vinylnapthalenewere obtained by diisobutylaluminum hydride reduction of thecorresponding nitrile [J. Am. Chem. Soc. 114, 6265 (1992)] followed bylithium aluminum hydride reduction. The relative assignments of theother hydroformylation products were assigned by analogy to be enrichedwith the S-enantiomer.

Typical Procedure for Hydroformylation Reactions

In the dry box a 140 mL glass liner was charged with 2.0 mmol of vinylcompound, 0.003 mmol of catalyst/cocatalyst, and 10 mL of solvent. Thisliner was placed in a shaker tube and pressurized with a 1:1 mixture ofhydrogen and carbon monoxide. After venting, the mixture was pressurizedwith the hydrogen, carbon monoxide mixture and shaken at the giventemperature. Upon completion, the mixture was vented and the glass linerwas removed from the shaker tube. The solution was filtered throughcelite and concentrated. Percent conversions were determined by ¹ H NMRintegration of the resonances corresponding to the starting vinylcompound and product aldehydes. The branched aldehyde to linear aldehyderatio (b/l) was determined by ¹ H NMR integration of the resonancescorresponding to the aldehyde protons or by GC.

The crude mixture was dissolved in 10 mL of ether and 50 mg (1.3 mmol)of LiAlH₄ was added. After 3 h, water (4 drops), 15% NaOH (4 drops) andwater (12 drops) was added carefully. After 30 min. Na₂ SO₄ was addedand the mixture was filtered and concentrated. Flash chromatography onsilica gel using 40% ether/hexane as eluant gave2-substituted-1-propanols. The ees of these alcohols were determined byanalysis on either an OB or OJ chiralcel HPLC column using ani-propanol/hexane mixture as eluant.

EXAMPLES 1-12 TABLES I AND II Hydroformylation of 2-VinylnapthaleneUsing Catalyst Composition 1 or 2 Example 1

Following the general procedure, a mixture of 300 mg (2.0 mmol) of2-vinylnapthalene and 5 mg of catalyst 1 in 10 mL of Et₃ SiH waspressurized at room temperature to 1600 psi using the H₂ /CO mixture.After 18 h, the mixture was manipulated as described: conversion=20%;b/l=22; ee=72%.

Example 2

The reaction was carried out similar to Example 1, using hexane assolvent and 500 psi of H₂ /CO provided the following: conversion=100%;b/l=20; ee=50%.

Example 3

The reaction was carried out similar to Example 1, using hexane andtriethylformate as solvent and 1600 psi of H₂ /CO provided thefollowing: conversion=85%; b/l=20; ee=17%. In this case the ee wasdetermined on the diethyl acetal resulting from in situ trapping of2-(2-napthyl)-1-propanal.

Examples 4-9 were performed in a similar fashion under the conditionsdescribed in Table I.

Examples 10-12 were performed in a similar manner using catalyst 2 underthe conditions described in Table II.

                  TABLE I                                                         ______________________________________                                        Asymmetric Hydroformylation                                                   of 2-Vinylnaphthalene Using Catalyst 1                                                        Pressure Temp.       Conv. ee                                 Ex.   Solvent   (psi)    (°C.)                                                                         b/l  (%)   (%)                                ______________________________________                                        1     Et.sub.3 SiH                                                                            1600     ambient                                                                              22    20   72                                 2     Hexane     500     ambient                                                                              20   100   49                                 3     Hexane +  1600     ambient                                                                              20    85   17                                       CH(OEt).sub.3                                                           4     Hexane    1600     ambient                                                                              26    53   51                                 5     Hexane    2400     ambient                                                                              24    80   31                                 6     Benzene   1600     ambient                                                                              33    43   38                                 7     THF       1600     ambient                                                                              40    71   12                                 8     THF       1600     70     11   100   10                                 9     THF       2400     ambient                                                                              --   100    7                                 ______________________________________                                    

                  TABLE II                                                        ______________________________________                                        Asymmetric Hydroformylation                                                   of 2-Vinylnaphthalene Using Catalyst 2                                                        Pressure Temp.       Conv. ee                                 Ex.   Solvent   (psi)    (°C.)                                                                         b/l  (%)   (%)                                ______________________________________                                        10    Benzene   1600     ambient                                                                              21    18   10                                 11    Benzene   1600     70     12   100    1                                 12    THF       1600     70     10   100   11                                 ______________________________________                                    

EXAMPLES 13-26 TABLE III

Examples 13-26 were performed in a similar fashion using the appropriatevinyl compound and catalyst as indicated. Abbreviations are as follows6-methoxy-2-vinylnapthalene (MVN), styrene (ST), 4-isobutylstyrene(IBS), 4-methylstyrene (4-MeST), vinyl acetate (VA). ##STR13##

                                      TABLE III                                   __________________________________________________________________________    Other Asymmetric Hydroformylation                                             Reactions Using L'Rh(COD)A Complexes                                                                       Conv.                                                                             ee                                           Ex.                                                                              Substrate                                                                           R.sup.1 A   Solvent                                                                            b/l                                                                              (%) (%)                                          __________________________________________________________________________    13 VN    (4-CF.sub.3)C.sub.6 H.sub.4                                                           BF.sub.4                                                                          Hexane                                                                             10 40  10                                           14 MVN   (4-CF.sub.3)C.sub.6 H.sub.4                                                           BF.sub.4                                                                          Hexane                                                                              8 10  15                                           15 MVN   4-FC.sub.6 H.sub.4                                                                    BF.sub.4                                                                          Hexane                                                                              7 10   5                                           16 VN    3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  SbF.sub.6                                                                         Hexane                                                                             18 100 19                                           17 ST    3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  BF.sub.4                                                                          Hexane                                                                             29 50  24                                           18 ST    3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  SbF.sub.6                                                                         Hexane                                                                             19 63  17                                           19 ST    3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  OT.sub.f                                                                          Hexane                                                                             21 53  14                                           20 4-MeST                                                                              3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  BF.sub.4                                                                          Hexane                                                                             16 43  30                                           21 IBS   3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  BF.sub.4                                                                          Et.sub.3 SiH                                                                       16  1  43                                           22 MVN   3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  BF.sub.4                                                                          Hexane                                                                             15 60  44                                           23 MVN   3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  BF.sub.4                                                                          Et.sub.3 SiH                                                                       20  5  70                                           24 MVN   3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  BF.sub.4                                                                          i-Pr.sub.3 SiH                                                                     14 14  16                                           25 VA    3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  BF.sub.4                                                                          Hexane                                                                             12 10  14                                           26 VA    3,5-(CF.sub.3).sub.2 C.sub.6 H.sub.3                                                  OTf Hexane                                                                              9 10  11                                           __________________________________________________________________________

EXAMPLES 27-30 Asymmetric Hydroformylation of6-Methoxy-2-vinylnapthalene and 2-Vinylnapthalene Using Chiral PlatinumCatalysts Example 27

Following the general procedure, a mixture of 400 mg (2.2 mmol) of6-methoxy-2-vinylnapthalene, 3 mg (0.016 mmol) of SnCl₂, 2 mg (0.016mmol) of 4-methoxyphenol and 10 mg (0.001 mmol) of {(phenyl[2,3-bis-O-(diphenylphosphino)]-4,6-benzylidene-β-D-glucopyranoside}platinum(II) dichloride (catalyst 7) in 10 mL of benzene was pressurized atambient temperature to 2400 psi using the H₂ /CO mixture. After 44 h,the mixture was manipulated as described: conversion=100%; b/l=0.7;ee=9%.

Example 28

The reaction was carried out similar to Example 31, except performingthe reaction at 60° C. which provided the following: conversion=100%;b/l=1.3; ee=9%.

Example 29

The reaction was carried cut similar to Example 31, using benzene andtriethylformate as solvent, which provided the following: %conversion=80%; b/l=1.5; ee=9%. In this case the ee was determined onthe diethyl acetal resulting from in situ trapping of2-(2-napthyl)-1-propanal.

Example 30

In this case a benzene solution of chiral platinum catalyst, (phenyl2,3-bis-O-{[di-(3,5-bis-trifluoromethyl)-phenyl]phosphino}-4,6-benzylidene-β-D-glucopyranoside)platinum(II)dichloride (catalyst 8), was generated from 24 mg (0.02 mmol) of 1 and 7mg (0.02 mmol) of dichlorobis(benzonitrile)platinum (II). This catalystsolution, 300 mg (2.0 mmol) of 2-vinylnapthalene, 6 mg (0.032 mmol) ofSnCl₂, 2 mg (0.016 mmol) of 4-methoxyphenol, and 8 mL of benzene wasplaced in a glass liner. The reaction was performed at 60° C. and 2400psi pressure of H₂ /CO for 18 h to provide the following:conversion=90%; b/l=2.7; ee=5%.

EXAMPLE 31 Asymmetric Hydroformylation of 6-Methoxy-2-vinylnapthaleneUsing Chiral Iridium Catalysts

The reaction was performed in a similar manner to the rhodium-catalyzedhydroformylations; 300 mg of MVN, 5 mg of chiral iridium catalyst 9, and10 mL of THF. This experiment was conducted at 80° C. using 3000 psi ofH₂ /CO to provide the following: conversion 37%; b/l=10; ee=30%.

EXAMPLE 32 Asymmetric Hydroformylation of 6-Methoxy-2-vinylnapthaleneUsing Chiral Cobalt Catalysts

This reaction was performed in a similar manner to the rhodium-catalyzedhydroformylations, except the chiral cobalt catalyst 10 was generated insitu from 4 mg of Co₂ (CO)₈ and 22 mg of 5 in 2 mL of THF. The reactionwas performed using this catalyst solution, 300 mg of MVN, and 8 mL ofTHF. The reaction was conducted at 120° C. and 5000 psi of H₂ /CO toprovide the following: conversion=10%; b/l=3; ee=1%.

What is claimed is:
 1. A catalyst composition comprising one or moremetals selected from the group consisting of Co, Rh, Ir and Pt, and achiral nonracemic ligand of formula II

    (R.sup.1).sub.2 --P--O--R.sup.2 --O--P--(R.sup.1).sub.2    II

wherein each R¹ is an electron-withdrawing group selected from the groupconsisting of an aromatic hydrocarbyl substituted with one or more halo,halogen-substituted alkyl groups, cyano, alkylsulfonyl, carboalkoxy,quaternary ammonium, nitro, amido or keto groups and a heteroaromaticoptionally substituted with one or more halo, halogen-substituted alkylgroups, cyano, alkylsulfonyl, carboalkoxy, quaternary ammonium, nitro,amido or keto groups; and R² is a C₄ to C₄₀ dideoxy carbohydrate;optionally substituted with one or more hydrocarbyl, halo, alkoxy,carboalkoxy, hydroxy, amido or keto groups.
 2. The composition of claim1, wherein the metal is Rh.
 3. The composition of claim 1, wherein theratio of ligand to metal is from about 1 to 1, to about 1.2 to
 1. 4. Thecomposition of claim 1, wherein R¹ is 3,5-(CF₃)₂ C₆ H₃.
 5. Thecomposition of claim 1, wherein R² is4,6-benzylidene-β-D-glycopyranoside.
 6. The composition of claim 1,wherein the metal is Rh and the ligand of formula II is phenyl2,3-bis-O-{[di-(3,5-bis-trifluoromethyl)-phenyl]phosphino}-4,6-benzylidene-β-D-glucopyranoside.